The long range goals of this project are to understand the mechanisms of action of the stem cell and undifferentiated spermatogonia in the mammalian testis; and to identify those factors which may regulate their behavior. This is of fundamental importance in male reproductive biology, since a continuing supply of spermatozoa throughout adult life ultimately depends upon the functional integrity of this spermatogonial population. Any disruption or malfunction of this compartment will have an expanding deleterious effect on the rest of the spermatogenic process. For this reason, the success of attempts to improve infertile conditions on the one hand, or to intelligently and irreversibly interrupt spermatogenesis for purposes of fertility control on the other hand, require a basic understanding of stem cell behavior. Baseline experiments to characterize mechanisms of action of sprmatogonia are not completed. We have seen that undifferentiated spermatogonia do alter their proliferative activities and rates of development in response to changes in hormonal environment and/or numbers of differentiating germ cells. We now begin work on our second objective, namely to search for specific regulatory factors. Initially, these studies will focus on the role of androgens in determining spermatogonial behavior. Specifically, we shall use morphological, quantitative and radioautographic tools to probe spermatogonial responses: 1) following administration of testosterone to regressed hypophysectomized rats; 2) during testosterone maintenance of the seminiferous epithelium in hypophysectomized rats; 3) to testosterone administration in normal adult rats; and 4) to testosterone treatment during repopulation of the irradiated adult germinal epithelium.